Geacintov N E, Zhao R, Kuzmin V A, Kim S K, Pecora L J
Chemistry Department, New York University, New York, NY 10003.
Photochem Photobiol. 1993 Aug;58(2):185-94. doi: 10.1111/j.1751-1097.1993.tb09547.x.
The hydrophobic interactions of bulky polycyclic aromatic hydrocarbons with nucleic acid bases and the formation of noncovalent complexes with DNA are important in the expressions of the mutagenic and carcinogenic potentials of this class of compounds. The fluorescence of the polycyclic aromatic residues can be employed as a probe of these interactions. In this work, the interactions of the (+)-trans stereoisomer of the tetraol 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (BPT), a hydrolysis product of a highly mutagenic and carcinogenic diol epoxide derivative of benzo[a]pyrene, were studied with 2'-deoxynucleosides in aqueous solution by fluorescence and UV spectroscopic techniques. Ground-state complexes between BPT and the purine derivatives 2'-deoxyguanosine (dG), 2'-deoxyadenosine (dA), and 2'-deoxyinosine (dI) are formed with association constants in the range of approximately 40-130 M(-1). Complex formation with the pyrimidine derivatives 2'-deoxythymidine (dT), 2'-deoxycytidine (dC), and 2'-deoxyuridine (dU) is significantly weaker. Whereas dG is a strong quencher of the fluorescence of BPT by both static and dynamic mechanisms (dynamic quenching rate constant k(DYN) = [2.5 +/- 0.4] x 10(9) M(-1)s(-1), which is close to the estimated diffusion-controlled value of approximately 5 x 10(9) M(-1)s(-1), both dA and dI are weak quenchers and form fluorescence-emitting complexes with BPT. The pyrimidine derivatives dC, dU, and dT are efficient dynamic fluorescence quenchers (k(DYN) approximately [1.5-3.0] x 10(9) M (-1)s(-1), with a small static quenching component due to complex formation evident only in the case of dT. None of the four nucleosides dG, dA, dC and dT are dynamic quenchers of BPT in the triplet excited state; the observed lower yields of triplets are attributed to the quenching of single excited states of BPT by 2'-deoxynucleosides without passing through the triplet manifold of BPT. Possible fluorescence quenching mechanisms involving photoinduced electron transfer are discussed. The strong quenching of the fluorescence of BPT by dG, dC and dT accounts for the low fluorescence yields of BPT-native DNA and of pyrene-DNA complexes.
大分子多环芳烃与核酸碱基的疏水相互作用以及与DNA形成非共价复合物，对于这类化合物诱变和致癌潜力的表达具有重要意义。多环芳烃残基的荧光可作为这些相互作用的探针。在本研究中，通过荧光和紫外光谱技术，研究了苯并[a]芘的一种高致突变和致癌二醇环氧化物衍生物的水解产物——四醇7,8,9,10 - 四羟基四氢苯并[a]芘（BPT）的(+)-反式立体异构体与2'-脱氧核苷在水溶液中的相互作用。BPT与嘌呤衍生物2'-脱氧鸟苷（dG）、2'-脱氧腺苷（dA）和2'-脱氧肌苷（dI）在基态形成复合物，缔合常数范围约为40 - 130 M⁻¹。与嘧啶衍生物2'-脱氧胸苷（dT）、2'-脱氧胞苷（dC）和2'-脱氧尿苷（dU）形成复合物的能力明显较弱。dG通过静态和动态机制都是BPT荧光的强猝灭剂（动态猝灭速率常数k(DYN) = [2.5 ± 0.4] × 10⁹ M⁻¹s⁻¹，接近估计的扩散控制值约5 × 10⁹ M⁻¹s⁻¹），而dA和dI都是弱猝灭剂，并与BPT形成发射荧光的复合物。嘧啶衍生物dC、dU和dT是有效的动态荧光猝灭剂（k(DYN)约为[1.5 - 3.0] × 10⁹ M⁻¹s⁻¹），只有在dT的情况下，由于复合物形成导致的静态猝灭成分较小才明显。四种核苷dG、dA、dC和dT都不是BPT三重激发态的动态猝灭剂；观察到的较低三重态产率归因于2'-脱氧核苷对BPT单重激发态的猝灭，而不经过BPT的三重态能级。讨论了涉及光诱导电子转移的可能荧光猝灭机制。dG、dC和dT对BPT荧光的强烈猝灭解释了BPT - 天然DNA和芘 - DNA复合物的低荧光产率。
